摘要目的:观察海南省新生儿苯丙酮尿症发病情况和苯丙氨酸羟化酶基因的分布特征。方法:收集2017年1月至2019年12月在海南省出生的380 996名新生儿足跟血干血斑样本，使用荧光法测定干血斑中苯丙氨酸的浓度，复筛使用串联质谱法检测新生儿重采干血斑样本中苯丙氨酸和酪氨酸的浓度；留取可疑患儿尿样本外送做尿蝶呤谱分析及四氢生物蝶呤负荷试验；使用核酸分子杂交仪利用PCR和导流杂交法检测干血斑样本苯丙氨酸羟化酶基因突变位点，同时抽取疑似患儿和父母外周血进行基因测序。结果:380 996名新生儿中初筛39例疑似患儿，确诊苯丙酮尿症14例，男8例，女6例，年发病率为1.22/10万。其中苯丙氨酸羟化酶缺乏症11例，四氢生物蝶呤缺乏症3例。共检出13个苯丙氨酸羟化酶基因位点突变：c.728G>A、c.158G>A、c.1238G>C、c.611A>G、c.1068C>A、c.706+5G>A、c.740G>T、c.1081A>T、c.793T>G、c.1223G>A、c.721C>T、c.331C>T和c.1174T>A。结论:最近3年内苯丙酮尿症在海南省新生儿人群发病率较高，苯丙氨酸羟化酶基因突变谱系多样，发现两种罕见的基因突变：c.793T>G和c.706+5G>A。

abstractsObjective:To investigate the incidence of phenylketonuria and distribution characteristics of phenylalanine hydroxylase (PAH) gene in newborns from Hainan province.Methods:Dry blood spot specimens of heels from 380 996 newborns in Hainan province from January 2017 to December 2019 were collected. Phenylalanine (Phe) concentrations in these dry blood spots were measured by the fluorescence method to screen phenylketonuria (PKU). A second dry blood spot sample will be collected if suspicious samples were detected after initial screening. Tandem mass spectrometry were used to detect the concentrations of Phe and tyrosine. Urine samples of the suspected newborns were sent out for urotrexate spectrum analysis and tetrahydrobiopterin loading test. PCR and flow-through rapid hybridization method were employed to detect PAH gene mutations. Meanwhile, peripheral blood samples of suspicious newborns of PKU and their parents were collected to perform gene sequencing.Results:Among the 380 996 newborns, 39 were suspected and 14 were diagnosed with PKU, including 11 cases of PAH deficiency and 3 cases of tetrahydrobiopterin deficiency. Of 14 confirmed cases, there were 8 male cases and 6 female cases. In the newborn population of Hainan province, the annual incidence of PKU was 1.22/100 000. Thirteen PAH gene mutations were detected in confirmed cases: c.728G>A, c.158G>A, c.1238G>C, c.611A>G, c.1068C>A, c.706+5G>A, c.740G>T, c.1081A>T, c.793T>G, c.1223G>A, c.721C>T, c.331C>T and c.1174T>A.Conclusions:PKU has a high incidence in newborn population of Hainan province in the past three years. The PAH gene has a wide spectrum of mutations. Two rare mutations were also found: c.793T>G and c.706+5G>A.